Aumento de la lipocalina orosomucoide-1 (ORM1) en sujetos con hiperaldosteronismo primario / Increase of lipocalin ORM1 in primary aldosteronism

El hiperaldosteronismo primario (HAP) es la causa más común de hipertensión arterial secundaria. A pesar de la prevalencia del HAP (6-10%) y sus consecuencias, los mecanismos que median los efectos deletéreos renales y extrarenales originados por la aldosterona más allá de la hipertensión arterial (ej. inflamación renal, alteraciones cardiacas y disfunción vascular), siguen siendo poco conocidos. Estudios previos sugieren que el exceso de aldosterona aumentaría proteínas sensibles a la activación del receptor de mineralocorticoides (MR), como las lipocalinas LCN2 (NGAL) y ORM1. OBJETIVO: Determinar la concentración de las lipocalinas ORM1, NGAL y NGAL-MMP9 en sujetos HAP. SUJETOS Y MÉTODOS: Estudio de cohorte transversal en sujetos adultos (similares en sexo, edad e IMC) separados en controles normotensos (CTL), hipertensos esenciales (HE) y con screening positivo de HAP (aldosterona ≥9 ng/dL y ARP < 1 ng/mL*h acorde a las guías internacionales de HAP). Se determinó la presión arterial sistólica (PAS) y diastólica (PAD), aldosterona plasmática, actividad renina plasmática (ARP) y la relación aldosterona / actividad de renina plasmática (ARR). Se determinó la concentración de NGAL, NGAL-MMP9 y ORM1 en suero por ELISA. RESULTADOS: Detectamos mayores niveles de ORM1 en sujetos HAP. No se detectaron diferencias en NGAL ni NGAL-MMP9 entre los grupos. Detectamos una asociación positiva de ORM1 con ARP (rho= -0,407, p=0,012) y con ARR (rho= 0,380 p= 0,021). CONCLUSIÓN: La mayor concentración de ORM1 en sujetos HAP y las asociaciones de ORM1 con aldosterona, ARP y ARR, proponen a esta proteína como un potencial biomarcador de HAP y de utilidad en el desarrollo de algoritmos diagnósticos de HAP.

Primary hyperaldosteronism (PA) is the most common cause of secondary hypertension. Despite the prevalence of PA (6-10%) and its consequences, the mechanisms that mediate the deleterious renal and extrarenal effects caused by aldosterone beyond arterial hypertension (eg renal inflammation, cardiac alterations and vascular dysfunction), remain barely known. Previous studies suggest that excess aldosterone would increase proteins sensitive to activation of the mineralocorticoid receptor (MR), such as lipocalins LCN2 (NGAL) and ORM1. AIM: To determine the concentration of the lipocalins ORM1, NGAL and NGAL-MMP9 in PA subjects. SUBJECTS AND METHODS: Cross-sectional study in adult subjects (similar in sex, age and BMI) grouped as normotensive controls (CTL), essential hypertensive (HE) and subjects with positive PA screening (aldosterone ≥ 9 ng/dL and PRA <1 ng/mL*h, according to international PA guidelines). Systolic (SBP) and diastolic (DBP) blood pressure, plasma aldosterone, plasma renin activity (PRA), and plasma aldosterone renin ratio (ARR) were determined. The concentration of NGAL, NGAL-MMP9 and ORM1 in serum was determined by ELISA. RESULTS: We detected higher levels Recibido: 03-09-2021 of ORM1 in PA subjects. No differences in NGAL or NGAL-MMP9 were detected between the groups. We detected a positive association of ORM1 with ARP (rho = -0.407, p < 0.05) and with ARR (rho = 0.380 p <0.05). CONCLUSION: The high levels of ORM1 in PA subjects and the associations of ORM1 with aldosterone, ARP and ARR, suggest ORM1 is a potential biomarker of PA, and useful in the development of a diagnostic algorithm for PA.

Urinary beta-trace protein gene expression analysis in type 2 diabetes mellitus patients / Análise da expressão do gene da proteína beta-traço na urina de pacientes com diabetes mellitus tipo 2

ABSTRACT Objective: To evaluate the gene expression of beta-trace protein in urine of diabetic patients, with no reduction in glomerular filtration rate, which was defined as below 60mL/min/1.73m2. Methods: Type 2 diabetes mellitus patients were recruited, and a group of non-diabetic individuals served as control. Beta-trace protein gene expression was analyzed by quantitative PCR. Blood samples were collected to establish glucose levels and baseline kidney function. Accuracy was analyzed using ROC curves. Results: Ninety type 2 diabetes mellitus patients and 20 non-diabetic individuals were recruited. The area under the curve was 0.601, sensitivity of 20% and specificity of 89.47%. Among diabetic participants, 18% showed an expression above the cutoff point. Conclusion: These results of accuracy of beta-trace protein gene expression in urine of diabetic patients are promising, although they did not achieve a higher area under the curve level.

RESUMO Objetivo: Avaliar a expressão do gene da proteína beta-traço na urina de pacientes diabéticos, sem redução na taxa de filtração glomerular, definida como abaixo de 60mL/min/1,73m2. Métodos: Foram recrutados pacientes com diabetes mellitus tipo 2, e um grupo de indivíduos não diabéticos serviu como controle. A expressão do gene da proteína beta-traço foi analisada por PCR quantitativa. Amostras de sangue foram coletadas para estabelecer níveis de glicemia e função renal inicial. A acurácia foi analisada utilizando curvas ROC. Resultados: Foram recrutados 90 pacientes com diabetes mellitus tipo 2 e 20 não diabéticos. A área sob a curva foi de 0,601, com sensibilidade de 20% e especificidade de 89,47%. Entre os diabéticos, 18% apresentaram expressão acima do ponto de corte. Conclusão: Estes resultados de acurácia da expressão do gene da proteína beta-traço na urina de pacientes diabéticos são promissores, apesar de não terem atingido um nível alto na área sob a curva.

Serum Chemerin Levels Are Associated with Abdominal Visceral Fat in Type 2 Diabetes

Chemerin is a recently identified adipokine suggested to play a role in obesity and its metabolic complications. The relationship between visceral obesity and serum chemerin levels in type 2 diabetes (T2DM) is unknown and may differ from that of subjects without diabetes. Therefore, we evaluated whether serum chemerin was associated with visceral abdominal obesity in patients with T2DM. A total of 218 Korean patients with T2DM were enrolled and metabolic parameters, abdominal visceral and subcutaneous fat areas, and serum chemerin levels were measured. Serum chemerin level showed positive correlation with fasting insulin, HOMA-IR, serum triglyceride, serum creatinine, urine albumin/creatinine ratio, high-sensitivity C-reactive protein (hsCRP), fibrinogen, abdominal visceral fat area, visceral to subcutaneous fat area ratio, and negatively correlation with high density lipoprotein cholesterol and creatinine clearance (CCr) after adjusting for age, gender and body mass index. Multiple linear stepwise regression analysis showed that abdominal visceral fat area (β = 0.001, P < 0.001), serum triglyceride (β = 0.001, P < 0.001), CCr (β = -0.003, P = 0.001), hsCRP (β = 0.157, P = 0.001), fibrinogen (β = 0.001, P < 0.001) and BMI (β = 0.02, P = 0.008) independently affected log transformed serum chemerin levels. Higher serum chemerin level was associated with higher level of abdominal visceral fat area, serum triglyceride, hsCRP and fibrinogen and lower level of CCr in patients with T2DM. Serum chemerin may be used as a biomarker of visceral adiposity and chemerin may play a role in inflammation, decreased renal function, and increased cardiovascular risk in T2DM.

Parecoxib reduces renal injury in an ischemia/reperfusion model in rats

PURPOSE: To evaluate the effect of parecoxib (an NSAID) on renal function by measuring plasma NGAL (serum neutrophil gelatinase-associated lipocalin) levels in an induced-ischemia rat model. METHODS: Forty male Wistar rats were randomly assigned to one of four groups: Ischemia (I), Ischemia/parecoxib (IP), No-ischemia (NI), and No-ischemia/parecoxib (NIP). Body weight, mean arterial pressure, heart rate, body temperature, NGAL levels, and renal histology were compared across groups. RESULTS: The Ischemia (I) group, which did not receive parecoxib, showed the highest NGAL levels (p=0.001), while the IP group, which received the medication, had NGAL levels similar to those of the non-ischemic (NI and NIP) groups. CONCLUSION: Parecoxib resulted in renal protection in this experimental model. .

Neutrophil gelatinase-associated lipocalin as a predictor of adverse renal outcomes in immunoglobulin A nephropathy

No abstract available.

Plasma neutrophil gelatinase-associated lipocalin as a potential predictor of adverse renal outcomes in immunoglobulin A nephropathy

BACKGROUND/AIMS: Neutrophil gelatinase-associated lipocalin (NGAL) is a well-known biomarker of acute kidney injury. We evaluated the value of plasma NGAL (pNGAL) as an independent predictor of prognosis in immunoglobulin A nephropathy (IgAN). METHODS: In total, 91 patients with biopsy-proven IgAN at a single center were evaluated. pNGAL was measured using a commercial enzyme-linked immunosorbent assay kit (R&D Systems). Adverse renal outcome was defined as chronic kidney disease (CKD) stage 3 or above at the last follow-up. Pearson correlation coefficient and Cox regression were used for analyses. RESULTS: The mean age of all patients (male:female, 48:43) was 35 years (range, 18 to 77). pNGAL ranged between 21.68 and 446.40 ng/mL (median, 123.97) and showed a correlation with age (r = 0.332, p = 0.001), creatinine (r = 0.336, p = 0.001), estimated glomerular filtration rate (r = -0.397, p 1 g/day (HR, 5.184; 95% CI, 1.124 to 23.921; p = 0.035), and pNGAL (HR, 1.012; 95% CI, 1.003 to 1.022; p = 0.013) were independent predictors associated with adverse renal outcome. CONCLUSIONS: pNGAL showed strong correlations with other clinical prognostic factors and was also an independent predictor of adverse renal outcome. We suggest pNGAL as a potential predictor for prognosis in IgAN, while further studies are needed to confirm the clinical value.

High serum and urine neutrophil gelatinaseassociated lipocalin levels are independent predictors of renal progression in patients with immunoglobulin A nephropathy

BACKGROUND/AIMS: Tubulointerstitial injury plays an important role in the progression of immunoglobulin A nephropathy (IgAN), and neutrophil gelatinase-associated lipocalin (NGAL) is among the most sensitive tubular biomarkers. We investigated whether serum or urine NGAL predicts prognosis in patients with IgAN. METHODS: The present study enrolled patients with biopsy-proven IgAN from January 2005 to December 2010, whose serum and urine samples at the time of kidney biopsy were preserved by freezing. We retrospectively reviewed patient clinical data and followed patients until October 2012. Serum and urine NGAL levels were measured using an enzyme-linked immunosorbent assay kit. Renal progression was defined as an estimated glomerular filtration rate decline by > 50% or progression to end-stage renal disease. RESULTS: There were 121 patients enrolled in this study. During the median follow-up period of 41.49 months, renal progression was found in nine patients (7.4%). Serum or urine NGAL alone could not predict renal progression; however, when serum and urine NGAL levels were combined, belonging to the high NGAL group independently predicted renal progression (hazard ratio [HR], 5.56; 95% confidence interval [CI], 1.42 to 21.73; p = 0.014), along with tubular damage graded according to the Oxford classification as T2 (HR, 8.79; 95% CI, 2.01 to 38.51; p = 0.004). In addition, a Kaplan-Meier curve of renal survival showed significantly higher renal progression in patients in the high NGAL group (log rank, p = 0.004). CONCLUSIONS: In patients with IgAN, high serum and urine NGAL levels at the time of kidney biopsy predict renal progression.

General anesthesia type does not influence serum levels of neutrophil gelatinase-associated lipocalin during the perioperative period in video laparoscopic bariatric surgery

OBJECTIVES: Video laparoscopic bariatric surgery is the preferred surgical technique for treating morbid obesity. However, pneumoperitoneum can pose risks to the kidneys by causing a decrease in renal blood flow. Furthermore, as in other surgical procedures, laparoscopic bariatric surgery triggers an acute inflammatory response. Neutrophil gelatinase-associated lipocalin is an early and accurate biomarker of renal injury, as well as of the inflammatory response. Anesthetic drugs could offer some protection for the kidneys and could attenuate the acute inflammatory response from surgical trauma. The objective of this study was to compare the effects of two types of anesthetics, propofol and sevoflurane, on the serum levels of neutrophil gelatinase-associated lipocalin during the perioperative period in laparoscopic bariatric surgery. METHODS: Sixty-four patients scheduled for laparoscopic bariatric surgery were randomized into two anesthesia groups and were administered either total intravenous anesthesia (propofol) or inhalation anesthesia (sevoflurane). In the perioperative period, blood samples were collected at three time points (before anesthesia, 6 hours after pneumoperitoneum and 24 hours after pneumoperitoneum) and urine output was measured for 24 hours. Acute kidney injuries were evaluated by examining both the clinical and laboratory parameters during the postoperative period. The differences between the groups were compared using non-parametric tests. ReBEC (http://www.ensaiosclinicos.gov.br/rg/recruiting/): RBR-8wt2fy RESULTS: None of the patients developed an acute kidney injury during the study and no significant differences were found between the serum neutrophil gelatinase-associated lipocalin levels of the groups during the perioperative period. CONCLUSION: The choice of anesthetic drug, either propofol or sevoflurane, did not affect the serum levels of neutrophil gelatinase-associated lipocalin during the perioperative ...

Evaluation of the Optimal Neutrophil Gelatinase-Associated Lipocalin Value as a Screening Biomarker for Urinary Tract Infections in Children

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is a promising biomarker in the detection of kidney injury. Early diagnosis of urinary tract infection (UTI), one of the most common infections in children, is important in order to avert long-term consequences. We assessed whether serum NGAL (sNGAL) or urine NGAL (uNGAL) would be reliable markers of UTI and evaluated the appropriate diagnostic cutoff value for the screening of UTI in children. METHODS: A total of 812 urine specimens and 323 serum samples, collected from pediatric patients, were analyzed. UTI was diagnosed on the basis of culture results and symptoms reported by the patients. NGAL values were measured by using ELISA. RESULTS: NGAL values were more elevated in the UTI cases than in the non-UTI cases, but the difference between the values were not statistically significant (P=0.190 for sNGAL and P=0.064 for uNGAL). The optimal diagnostic cutoff values of sNGAL and uNGAL for UTI screening were 65.25 ng/mL and 5.75 ng/mL, respectively. CONCLUSIONS: We suggest that it is not appropriate to use NGAL as a marker for early diagnosis of UTI in children.

Biomarcadores da injúria renal aguda / Biomarkers of acute kidney injury

A creatinina continua a ser o padrão laboratorial para diagnóstico da injúria renal aguda (IRA). Esforços para prevenção da nefrotoxicidade foram prejudicados pelo atraso no diagnóstico da IRA por critérios utilizando somente a creatinina como marcador, havendo, por isso, grande interesse em identificar mais precocemente biomarcadores confiáveis. Além disso, o tratamento precoce da IRA pode ser correlacionado com um melhor prognóstico e a identificação de biomarcadores para um diagnóstico precoce pode melhorar a eficácia de estratégia terapêutica. Portanto, torna-se imperativo encontrar biomarcadores que possam estratificar corretamente o grau de lesão renal e o risco de desenvolver doença renal crônica (DRC). Aqui, nós revisamos as principais características dos emergentes biomarcadores em nefrologia.

Creatinine remains the standard for laboratory diagnosis of AKI. Efforts to prevent nephrotoxicity have been harmed by the delay in the diagnosis of AKI criteria by using only the creatinine as a marker, therefore there is great interest in identifying early reliable biomarkers. Moreover, early treatment of ARF can be correlated with a better prognosis and identification of biomarkers for early diagnosis would improve the efficacy of a therapeutic strategy. Thus, it becomes imperative to find biomarkers that can stratify correctly the extent of renal damage that each patient has suffered and the risk of developing chronic kidney disease (CKD). Here, we review the main features of emerging biomarkers in nephrology.

The effect of 6% Hydroxyethyl starch vs. Ringer's lactate on acute kidney injury after renal ischemia in rats

PURPOSE: To compare fluid replacement therapy with Hydroxyethyl starch 6% (HES) versus Ringer's lactate (RL) in a rodent model of non-septic renal ischemia. METHODS: Forty male Wistar rats were randomized to receive HES 2 ml.kg-1.hr-1or RL 5 ml. kg-1.hr-1 that underwent 30 minutes of renal ischemia followed by reperfusion. Twelve hours after kidney ischemia, the kidneys were evaluated for histological changes. Serum NGAL levels were obtained at different times of the experimental protocol. RESULTS: Rodents in the HES group had a median (IQR) grade of renal injury 3 (3 to 5) compared to 2 (2 to 4) in the RL group (p=0.03). NGAL levels were not associated with the severity of kidney injury. CONCLUSION: Hydroxyethyl starch administration caused more kidney injury than Ringer's lactate in a non-infectious model of renal hypoperfusion.

New Biomarkers of Acute Kidney Injury and the Cardio-renal Syndrome / 대한진단검사의학회지

Changes in renal function are one of the most common manifestations of severe illness. There is a clinical need to intervene early with proven treatments in patients with potentially deleterious changes in renal function. Unfortunately progress has been hindered by poor definitions of renal dysfunction and a lack of early biomarkers of renal injury. In recent years, the definitional problem has been addressed with the establishment of a new well-defined diagnostic entity, acute kidney injury (AKI), which encompasses the wide spectrum of kidney dysfunction, together with clearer definition and sub-classification of the cardio-renal syndromes. From the laboratory have emerged new biomarkers which allow early detection of AKI, including neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C. This review describes the new concepts of AKI and the cardio-renal syndromes as well as novel biomarkers which allow early detection of AKI. Panels of AKI biomarker tests are likely to revolutionise the diagnosis and management of critically ill patients in the coming years. Earlier diagnosis and intervention should significantly reduce the morbidity and mortality associated with acute kidney damage.